Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.21.1 (DNase)
7,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The prevalence, quantity, temporal pattern, and clinical and immunologic correlates of shedding of Kaposi's sarcoma (KS)-associated herpesvirus (KSHV; or human herpesvirus [HHV]-8) DNA in saliva were studied. KSHV DNA was detected in saliva from 18 (75%) of 24 human immunodeficiency virus (HIV)-positive patients with KS and from 1 of 1 HIV-negative patient with KS, 3 (15%) of 20 HIV-positive patients without KS, and none of 24 controls. KSHV DNA levels ranged from 10(2.4) to 10(6) copies/mL and were lower than levels for Epstein-Barr virus but comparable to those for HHV-6. Detection of KSHV DNA in saliva was not associated with oral KS or decreased peripheral blood CD4 cell counts. KSHV DNA was not detected in semen. Resistance of KSHV DNA from saliva to DNase treatment was consistent with the presence of virions. These data suggest that KSHV can replicate in the oropharynx and that salivary contact could contribute to KSHV transmission.
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PMID:Frequent detection of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) DNA in saliva of human immunodeficiency virus-infected men: clinical and immunologic correlates. 920 54

We found and previously reported a new mammalian DNA polymerase inhibitor from a sea alga, Gigartina tenella, (Ohta K., et al., Chem. Pharm. Bull., 46, 684-686, 1998). It was a new sulfolipid compound that belonged in the class of sulfoquinovosyldiacylglycerol. The biochemical properties have been investigated here. The compound, temporarily designated KM043, potently inhibited the activities of mammalian DNA polymerase alpha(pol. alpha) and DNA polymerase beta(pol. beta) and terminal deoxynucleotidyl transferase (TdT), and moderately, human immunodeficiency virus reverse transcriptase (HIV-RT). KM043 dose-dependently inhibited their activities, and each of their IC50 values was 0.25 microM for pol. alpha, 0.38 microM for TdT, 3.6 microM for pol. beta, or 11.2 microM for HIV-RT, and almost complete inhibition of each was achieved at 1.0 to 2.0 microM for pol. alpha and TdT, 7.5 microM for pol. beta and about 30 microM for HIV-RT. However, the compound did not influence the activities of prokaryotic DNA polymerases such as E. coli DNA polymerase I, and DNA metabolic enzymes like DNase 1. Inhibition of pol. alpha or beta by KM043 was non-competitive with both the DNA template and the substrate deoxythymidine 5'-triphosphate (dTTP). KM043 was weakly cytotoxic to cultured HeLa-S3 cells, and the IC50 value was 80 microM. KM043 could synergistically enhance the cytocidal effect of an anti-cancer chemotherapy agent, bleomycin. In the presence of 50 microM KM043, the effect ratio of (bleomycin plus KM043)/(bleomysin only) decreased from 0.76 to 0.22.
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PMID:Action of a new mammalian DNA polymerase inhibitor, sulfoquinovosyldiacylglycerol. 1007 26

Terpenoids, 1, 2 and 3, which selectively inhibit eukaryotic DNA polymerase activities, were isolated from the fruiting body of a basidiomycete, Ganoderma lucidum, and their structures were determined by spectroscopic analyses. New terpenes, lucidenic acid O (1) and lucidenic lactone (2), prevented not only the activities of calf DNA polymerase alpha and rat DNA polymerase beta, but also these of human immunodeficiency virus type 1 reverse transcriptase. Cerevisterol (3), which was reported to be a cytotoxic steroid, inhibited only the activity of DNA polymerase alpha. Although these compounds did not influence the activities of prokaryotic DNA polymerases and other DNA metabolic enzymes such as T7 RNA polymerase and deoxyribonuclease I.
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PMID:Lucidenic acid O and lactone, new terpene inhibitors of eukaryotic DNA polymerases from a basidiomycete, Ganoderma lucidum. 1053 Sep 54

We developed a technique with which to isolate specific subchromatin deoxyribonucleoprotein/ribonucleoprotein precursor complexes containing discrete genes from intact mammalian nuclei by direct restriction enzyme treatment with MspI. These nucleoprotein complexes can be further fractionated and purified by two-dimensional isoelectric focusing/sodium dodecyl sulfate-polyacrylamide gel electrophoresis. After electroelution and removal of detergent, virtually thousands of nucleoprotein complexes can be examined for the presence of tightly bound genes and enzymatic activities. Nucleoprotein gene tracking procedures were applied to study the acidic nucleoprotein complexes from steady-state human H9 cells uninfected or infected with human immunodeficiency virus type 1 (HIV-1) virus. The purified nucleoprotein complexes were screened for the presence of loosely and tightly associated HIV-1 gene sequences (pol, env, tat, and rev) using a DNA hybridization protocol. In HIV-1-infected cells, four specific nucleoprotein complexes out of several hundred were found to contain tightly bound HIV-1 pol gene sequences after purification. By contrast, the other HIV-1 gene sequences (env, tat, and rev) were not tightly bound to any of the nucleoprotein complexes in HIV-infected cells. The observations suggest that certain HIV-1 genes associate with specific chromatin nucleoprotein complexes, regardless of their pattern of DNA integration into the human genome. At least two of the HIV-1 pol-containing nucleoprotein complexes of apparent M(r) approximately 94,000, pI approximately 6.5, and M(r) approximately 47,000, pI approximately 5.1 contain DNA endonuclease activity. This was confirmed in the present study, using linearized pUC19 plasmid substrate. The technique can be used to study a variety of problems concerning the association of specific genes and enzymes with specific nucleoprotein complexes J. Cell. Biochem. Suppls. 32/33:158-165, 1999.
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PMID:Nucleoprotein gene tracking: localization of specific HIV-1 genes to subchromatin nucleoprotein complexes containing endonuclease activity in HIV-1-infected human cells. 1062 15

As described previously, we found that new triterpenoid compounds, designated fomitellic acids A and B, which selectively inhibit the activities of mammalian DNA polymerases alpha and beta [Mizushina, Tanaka, Kitamura, Tamai, Ikeda, Takemura, Sugawara, Arai, Matsukage, Yoshida and Sakaguchi (1998) Biochem. J. 330, 1325-1332; Tanaka, Kitamura, Mizushina, Sugawara and Sakaguchi (1998) J. Nat. Prod. 61, 193-197] and that a known triterpenoid, ursolic acid, is an inhibitor of human DNA topoisomerases I and II (A. Iida, Y. Mizushina and K. Sakaguchi, unpublished work). Here we report that all of these triterpenoids are potent inhibitors of calf DNA polymerase alpha, rat DNA polymerase beta and human DNA topoisomerases I and II, and show moderate inhibitory effects on plant DNA polymerase II and human immunodeficiency virus reverse transcriptase. However, these compounds did not influence the activities of prokaryotic DNA polymerases such as Escherichia coli DNA polymerase I or other DNA metabolic enzymes such as human telomerase, T7 RNA polymerase and bovine deoxyribonuclease I. These triterpenoids were not only mammalian DNA polymerase inhibitors but also inhibitors of DNA topoisomerases I and II even though the enzymic characteristics of DNA polymerases and DNA topoisomerases, including their modes of action, amino acid sequences and three-dimensional structures, differed markedly. These triterpenoids did not bind to DNA, suggesting that they act directly on these enzymes. Because the three-dimensional structures of fomitellic acids were shown by computer simulation to be very similar to that of ursolic acid, the DNA-binding sites of both enzymes, which compete for the inhibitors, might be very similar. Fomitellic acid A and ursolic acid prevented the growth of NUGC cancer cells, with LD(50) values of 38 and 30 microM respectively.
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PMID:Novel triterpenoids inhibit both DNA polymerase and DNA topoisomerase. 1097 Jul 89

The glycolipid galactosyldiacylglycerol (GDG), containing C16:0 and C18:1 fatty acids, was isolated from the sea alga Petalonia bingbamiae as a potent inhibitor of the activities of mammalian DNA polymerase alpha (pol. alpha). GDG, however, had no effect on pol. alpha from a fish or a higher plant. The inhibition of pol. alpha by GDG was dose-dependent with an IC50 value of 54 microM. The compound did not influence the activities of other replicative DNA polymerases such as mammalian pol. delta, or repair-related enzymes such as mammalian pol. beta. GDG also did not influence the activities of prokaryotic DNA polymerases such as the Klenow fragment of DNA polymerase I, T4 DNA polymerase, Taq DNA polymerase, DNA polymerases from the higher plant, cauliflower, or DNA metabolic enzymes such as calf thymus terminal deoxynucleotidyl transferase, human immunodeficiency virus type 1 reverse transcriptase and deoxyribonuclease 1. Kinetic analysis of the compound showed that pol. alpha was non-competitively inhibited with respect to both the DNA template and the nucleotide substrate. In this study, we demonstrated the structure-function relationship in the selective inhibition of pol. alpha by the glycolipid group.
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PMID:Galactosyldiacylglycerol, a mammalian DNA polymerase alpha-specific inhibitor from a sea alga, Petalonia bingbamiae. 1155 81

(R)-(-)-Elenic acid (R-2,4-dimethyl-22-(p-hydroxyphenyl)-docos-3(E)-enoic acid) (EA) is a DNA topoisomerase II inhibitor found in an Indonesian sponge, Plakinastrella sp. We found and report here that it is a potent inhibitor of calf DNA polymerase alpha (IC(50)=7.7 microM) and rat DNA polymerase beta (IC(50)=12.9 microM). EA did not bind to DNA directly. EA did not influence the activities of DNA polymerases such as plant DNA polymerases I and II and prokaryotic DNA polymerases such as Escherichia coli DNA polymerase I, or other DNA metabolic enzymes such as human immunodeficiency virus (HIV) reverse transcriptase, T7 RNA polymerase and bovine deoxyribonuclease I. Interestingly, EA was also an inhibitor of DNA topoisomerases I and II, although the enzymatic characteristics including modes of action, amino acid sequences and three-dimensional structures were markedly different from those of DNA polymerases. EA could prevent the growth of NUGC-3 cancer cells, and the LD(50) value was 22.5 microM. The cells were halted at G1 and G2/M phase in the cell cycle. From these results, the action mode of EA is discussed.
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PMID:Selective inhibition of the activities of both eukaryotic DNA polymerases and DNA topoisomerases by elenic acid. 1185 91

Retinoic acids, vitamin A-related compounds, are known to be inhibitors of telomerase. We found that fucoxanthin from the sea alga Petalonia bingamiae is a potent inhibitor of mammalian replicative DNA polymerases (i.e., pol alpha, delta and epsilon). Since fucoxanthin is a carotenoid (provitamin A-related) compound, we characterized the biochemical modes of vitamin A-related compounds including vitamin A and provitamin A in this report. Subsequently, we found that fucoxanthin, all-trans retinal (RAL, vitamin A aldehyde) and all-trans retinoic acid (RA, vitamin A acid) inhibited the activities of replicative DNA polymerases with IC(50) values of 18-190, 14-17 and 8-30 microM, respectively. On the other hand, all-trans retinol (vitamin A) did not influence any of the DNA polymerase activities. RA inhibited not only the activities of pol alpha, delta and epsilon with IC(50) values of 30, 28 and 8 microM, respectively, but of pol beta with an IC(50) value of 27 microM. The tested vitamin A-related compounds did not influence the activities of DNA polymerases from a higher plant, cauliflower, prokaryotic DNA polymerases, or DNA metabolic enzymes such as human immunodeficiency virus type 1 reverse transcriptase, T7 RNA polymerase and bovine deoxyribonuclease I. RAL and RA should be called selective inhibitors of mammalian DNA polymerases including telomerase, and RAL was a specific inhibitor of mammalian replicative DNA polymerases. As expected from these results in vitro, some of them could prevent the growth of NUGC-3 human gastric cancer cells, and especially RAL was a potent antineoplastic agent with an LD(50) value of 19 microM. The cells were halted at G1 phase in the cell cycle by RAL.
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PMID:Vitamin A-related compounds, all-trans retinal and retinoic acids, selectively inhibit activities of mammalian replicative DNA polymerases. 1195 16

Two flavonoid glycosides, kaempferol 3-O-(6"-acetyl)-beta-glucopyranoside (KAG) and quercetin 3-O-(6"-acetyl)-beta-glucopyranoside (QAG), were found to be inhibitors of eukaryotic DNA polymerases from a Japanese vegetable, Petasites japonicus. These compounds inhibited the activities of mammalian replicative DNA polymerases (i.e., pol alpha, delta, and epsilon), but not other pol beta, eta, kappa, and lambda activities. KAG was a stronger inhibitor and more selective to pol alpha than QAG. The IC(50) values of KAG for pol alpha, delta, and epsilon were 41, 164, and 127 microM, respectively. The pol alpha inhibition by KAG was non-competitive with respect to both the DNA template-primer and the dNTP substrate. KAG and QAG did not influence the activities of prokaryotic DNA polymerases or other mammalian DNA metabolic enzymes such as human immunodeficiency virus type 1 reverse transcriptase, human telomerase, human DNA topoisomerase I and II, T7 RNA polymerase, and bovine deoxyribonuclease I. Therefore, we concluded that these flavonoid glycosides are moderate replicative DNA polymerase inhibitors leaning more relatively to pol alpha, and could be used as chromatographic carriers to purify the DNA polymerases rather than cytotoxic agents. We then made a KAG-conjugated column such as the epoxy-activated Sepharose 6B. In the column, pol alpha was selectively adsorbed and eluted.
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PMID:Flavonoid glycoside: a new inhibitor of eukaryotic DNA polymerase alpha and a new carrier for inhibitor-affinity chromatography. 1256 87

The pyrrolidine alkaloids mimicking the structures of pentose with nitrogen in the ring are known to be inhibitors of glycosidases. We report here that a compound belonging to this category is an inhibitor of eukaryotic DNA polymerases. Among the eight naturally occurring pyrrolidine alkaloids we tested, only one compound, 1,4-dideoxy-1,4-imino-D-ribitol (DRB), which was purified from the mulberry tree (Morus alba), strongly inhibited the activities of eukaryotic DNA polymerases with IC50 values of 21-35 microM, and had almost no effect on the activities of prokaryotic DNA polymerases, nor DNA metabolic enzymes such as human immunodeficiency virus type 1 reverse transcriptase, T7 RNA polymerase, and bovine deoxyribonuclease I. Kinetic studies showed that inhibition of both DNA polymerases alpha and beta by DRB was competitive with respect to dNTP substrate. Whereas DNA polymerase alpha inhibition was noncompetitive with the template-primer, the inhibition of DNA polymerase beta was found to be competitive with the template-primer. The K(i) values of DNA polymerases alpha and beta for the template-primer were smaller than those for dNTP substrate. Therefore, the affinity of DRB was suggested to be higher at the template-primer binding site than at the dNTP substrate-binding site, although DRB is an analogue of deoxyribose consisting of dNTP. Computational analyses of the eight pyrrolidine alkaloids revealed a remarkable difference in the distribution of positive and negative electrostatic charges on the surface of molecules. The relationship between the structure of DRB and the inhibition of eukaryotic DNA polymerases is discussed.
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PMID:The inhibitory action of pyrrolidine alkaloid, 1,4-dideoxy-1,4-imino-D-ribitol, on eukaryotic DNA polymerases. 1270 87


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